Many cellular functions are modulated by the concentration of intracellular calcium ions. Specifically, calcium ions act as intracellular messengers that regulate the functions of cells in many living systems. Two major receptor mechanisms of calcium mobilization are known that utilize calcium stored in cytoplasmic compartments for signaling. In epithelial and blood cells, the predominant mechanism of Ca.sup.2+ release is triggered by the interaction of the second messenger, inositol 1,4,5-triphosphate (IP.sub.3), with its receptor, a ligand-activated calcium-selective channel. The binding of IP.sub.3 promotes channel opening, allowing Ca.sup.2+ to flow into the cytoplasm.
A second class of intracellular calcium-releasing channels is the ryanodine receptor. These receptors are present in muscle and brain and may be activated by the plant alkaloid, ryanodine, and caffeine. Although the physiological activator of the ryanodine receptor is unknown, it can be activated by Ca.sup.2+, causing the so called Ca.sup.2+ -induced Ca.sup.2+ release (CICR). One ryanodine activator candidate is a metabolite of .beta.-NAD.sup.+, cyclic ADP-ribose (cADPR), which was shown to be as potent as IP.sub.3 in mobilizing intracellular Ca.sup.2+ stores in sea urchin eggs and in rat pituitary cells. cADPR has the following structure: ##STR1## The widespread occurrence of the ryanodine receptor and cADPR in mammalian tissues suggests that cADPR may be an endogenous messenger for ryanodine receptors. Several other recent studies are consistent with this proposition.